Assays for TSE agents vary substantially in sensitivity, range of agents detected and time required to detect agents. More promising assay methods should be optimized for use in TSE-agent surveillance programs. Transgenic (Tg) mice expressing the prion-protein genes of more susceptible species show great promise as assay animals for detecting the agents of transmissible spongiform encephalopathies (TSEs). The Laboratory of Method Development, DVP, OVRR, CBER has proposed to establish a program to compare the sensitivity of candidate lines of Tg mice to detect various TSE agents. We will obtain-from collaborators in NIAID-PrP-knock-out mice into which transgenes expressing ovine, bovine or human prion-protein open reading frames including one or more of those mutations thought to increase susceptibility to TSE agents and linked to neuron-specific promoter genes~~will be introduced. This must be a long-term effort, but the start-up costs for establishing the small breeding groups of Tg mice and assembling the TSE agent strains to compare in those mice is by far the most difficult and expensive part of the project. This project was selected for support as fulfilling "unmet needs" by OD CBER. In FY 97 three reference strains of scrapie agent and one of mouse adapted Creutzfeldt-Jakob disease agent were obtained and archived. In FY 98 working stocks of TSE agent strains were prepared adnd titrated. An ORISE fellow was recruited to assist in aspects of the project. This project will be continued in FY 99.